A three-step support strategy for relatives of patients dying in the intensive care unit: a cluster randomised trial.

BACKGROUND: In relatives of patients dying in intensive care units (ICUs), inadequate team support can increase the prevalence of prolonged grief and other psychological harm. We aimed to evaluate whether a proactive communication and support intervention would improve relatives' outcomes. METHODS: We undertook a prospective, multicentre, cluster randomised controlled trial in 34 ICUs in France, to compare standard care with a physician-driven, nurse-aided, three-step support strategy for families throughout the dying process, following a decision to withdraw or withhold life support. Inclusion criteria were relatives of patients older than 18 years with an ICU length of stay 2 days or longer. Participating ICUs were randomly assigned (1:1 ratio) into an intervention cluster and a control cluster. The randomisation scheme was generated centrally by a statistician not otherwise involved in the study, using permutation blocks of non-released size. In the intervention group, three meetings were held with relatives: a family conference to prepare the relatives for the imminent death, an ICU-room visit to provide active support, and a meeting after the patient's death to offer condolences and closure. ICUs randomly assigned to the control group applied their best standard of care in terms of support and communication with relatives of dying patients. The primary endpoint was the proportion of relatives with prolonged grief (measured with PG-13, score ≥30) 6 months after the death. Analysis was by intention to treat, with the bereaved relatives as the unit of observation. The study is registered with ClinicalTrials.gov, NCT02955992. FINDINGS: Between Feb 23, 2017, and Oct 8, 2019, we enrolled 484 relatives of ICU patients to the intervention group and 391 to the control group. 379 (78%) relatives in the intervention group and 309 (79%) in the control group completed the 6-month interview to measure the primary endpoint. The intervention significantly reduced the number of relatives with prolonged grief symptoms (66 [21%] vs 57 [15%]; p=0·035) and the median PG-13 score was significantly lower in the intervention group than in the control group (19 [IQR 14-26] vs 21 [15-29], mean difference 2·5, 95% CI 1·04-3·95). INTERPRETATION: Among relatives of patients dying in the ICU, a physician-driven, nurse-aided, three-step support strategy significantly reduced prolonged grief symptoms. FUNDING: French Ministry of Health.

Performance of Diagnostic Scores in Thrombotic Microangiopathy Patients in the Intensive Care Unit: A Monocentric Study.

Early thrombotic thrombocytopenic purpura (TTP) recognition is critical as this disease is almost always lethal if not treated promptly with therapeutic plasma exchanges. Currently, as ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity is not widely available in emergency, scores have been developed to help differentiating TTP from other thrombotic microangiopathies (TMAs). The aim of this work was to study the accuracy of these diagnostic scores in the intensive care unit (ICU) setting. Performance of both Coppo and PLASMIC scores was studied in a cohort of adult TMA patients requiring admission to one university hospital ICU from 2006 to 2017. Receiver operating characteristic (ROC) curves were established, and confidence intervals of the area under the curve (AUC) were determined. Multivariate logistic regression analysis was performed to identify parameters specifically associated with TTP, to compare diagnostic scores and to elaborate more accurate diagnostic models. During the study period, 154 TMA patients required ICU admission, including 99 (64.2%) TTP and 55 (35.7%) non-TTP patients. AUC under the ROC curve in predicting TTP was 0.86 (95% confidence interval [CI]: 0.81-0.92) for the Coppo score, 0.67 (95% CI: 0.58-0.76) for the PLASMIC score, and 0.86 (95% CI: 0.81-0.92) for platelet count alone. Platelet count ≤20 G/L, determined as the best cut-off rate for thrombocytopenia, performed similarly to the Coppo score and better than the PLASMIC score to differentiate TTP from non-TTP patients, both using AUC ROC curve and logistic regression. In a monocentric cohort of TMA patients requiring ICU admission, the PLASMIC score had limited performance for the diagnosis of TTP. The performance of the Coppo score was good but similar to a single highly discriminant item: platelet count ≤20 G/L at admission.

Epidemiology, clinical features, and management of severe hypercalcemia in critically ill patients.

BACKGROUND: Severe hypercalcemia (HCM) is a common reason for admission in intensive-care unit (ICU). This case series aims to describe the clinical and biological features, etiologies, treatments, and outcome associated with severe HCM. This study included all patients with a total calcemia above 12 mg/dL (3 mmol/L) admitted in two ICUs from January 2007 to February 2017. RESULTS: 131 patients with HCM were included. HCM was related to hematologic malignancy in 58 (44.3%), solid tumors in 29 (22.1%), endocrinopathies in 16 (12.2%), and other causes in 28 (21.3%) patients. 108 (82.4%) patients fulfilled acute kidney injury (AKI) criteria. Among them, 25 (19%) patients required renal replacement therapy (RRT). 51 (38.9%) patients presented with neurological symptoms, 73 (55.7%) patients had cardiovascular manifestations, and 50 (38.1%) patients had digestive manifestations. The use of bisphosphonates (HR, 0.42; 95% CI, 0.27-0.67; P < 0.001) was the only treatment significantly associated with a decrease of total calcemia below 12 mg/dL (3 mmol/L) at day 5. ICU and Hospital mortality rates were, respectively, 9.9% and 21.3%. Simplified Acute Physiologic Score (SAPS II) (OR, 1.05; 95% CI 1.01-1.1; P = 0.03) and an underlying solid tumor (OR, 13.83; 95% CI 2.24-141.25; P = 0.01) were two independent factors associated with hospital mortality in multivariate analysis. CONCLUSIONS: HCM is associated with high mortality rates, mainly due to underlying malignancies. The course of HCM may be complicated by organ failures which are most of the time reversible with early ICU management. Early ICU admission and prompt HCM management are crucial, especially in patients with an underlying solid tumor presenting with neurological symptoms.

Invasive pulmonary aspergillosis in critically ill patients with hematological malignancies.

PURPOSE: Invasive pulmonary aspergillosis (IPA) is a dreadful event in patients with hematological malignancies (HM). Recent advances have standardized diagnostic, prophylactic and curative therapeutic strategies. We sought to assess whether these advances actually translate into improved survival in critically ill patients with acute respiratory failure and IPA. METHODS: This was a retrospective, multicenter study. Adult patients with HM, IPA, admitted to the ICU for acute respiratory failure over a 20-year period (January 1998-December 2017) were included. A cox regression model was used to identify variables independently associated with day-90 survival. RESULTS: Overall, 219 patients were included [138 (63%) men, median age 55 (IQR 44-64)]. Acute myeloid leukemia (30.1%) and non-Hodgkin lymphoma (22.8%) were the most frequent malignancies, and 53 (24.2%) were allogeneic stem cell recipients. Day-1 SOFA score was 9 [7-12]. Most patients presented with probable IPA, whereas 15 (7%) underwent lung biopsies or pleurocentesis and met criteria for proven IPA. Overall ICU and day-90 mortality were, respectively, 58.4% and 75.2% (80.4% if invasive mechanical ventilation) without any significant improvement over time. By multivariable analysis adjusted on day-1 SOFA score and ventilation strategies, voriconazole use (HR 0.49, CI 95 0.34-0.73, p < 0.001) and an ICU admission after 2010 (HR 0.67, 0.45-0.99, p = 0.042) were associated with increased survival, whereas a diffuse radiologic pattern (HR 2.07, CI 95 1.33-3.24, p = 0.001) and delayed admission to the ICU (HR 1.51, CI 95 1.05-2.16, p = 0.026) were independently associated with increased mortality. CONCLUSIONS: IPA is associated with high mortality rates in critically ill patients with acute respiratory failure. Routine voriconazole and prompt ICU admission are warranted.

Candidemia in critically ill immunocompromised patients: report of a retrospective multicenter cohort study.

BACKGROUND: Immunocompromised critically ill patients constitute a population with the high risk of candidemia. This retrospective study aimed to assess the outcome of immunocompromised critically ill patients with candidemia. Secondary objectives were to describe clinical phenotypes of these patients, Candida ecology, and factors associated with mortality. RESULTS: Overall, 121 patients were included in this study. Median delay from candidemia to first antifungal therapy was 3 days, in line with the observed delay of blood culture positivity. Candia albicans was the main Candida specie identified (54%), and susceptibility of Candida to fluconazole and echinocandins was of, respectively, 70% and 92%. Hospital mortality was of 60%. After adjustment for confounders, severity as assessed by the need for vasopressors (HR 1.8, CI95% 1.1-3.1), need for mechanical ventilation (HR 2.0, CI95% 1.1-3.8) and allogenic stem cell transplantation (HR 2.5, CI95% 1.1-6.0) were independently associated with poor outcome. Candida specie, susceptibility and treatment strategies were not associated with outcome. CONCLUSIONS: Candidemia in immunocompromised critically ill patients is associated with a grim outcome. Despite the high prevalence of Candida non-albicans species, neither C. species nor its susceptibility was associated with outcome. Conversely, severity and preexisting allogeneic stem cell transplantation were independently associated with poor outcome. Despite antifungal prophylaxis and use of preemptive antifungal therapy in neutropenic patients, antifungal therapy was initiated three days after symptoms onset suggesting needs for specific strategies aiming to reduce this delay.

Acute kidney injury in critically ill patients with solid tumours.

Background: Patients with solid tumours are at risk for acute kidney injury (AKI), however, epidemiological data are limited. Methods: We conducted a study that included patients with solid tumours admitted to a single-centre intensive care unit (ICU) from January 2011 to December 2015. We analysed factors associated with the occurence of AKI, ICU and Day-90 mortality. Results: Two-hundred and four patients were included. The incidence of AKI was 59%, chiefly related to sepsis (80%), hypovolaemia (40%) and outflow tract obstruction (17%). Renal replacement therapy was implemented in 12% of the patients, with a hospital mortality of 39%. Independent predictors of AKI were: Simplified Acute Physiological Score II (SAPS II) [odds ratio (OR) 1.05; 95% confidence interval (95% CI) 1.02-1.07; P < 0.001], abdominal or pelvic cancer (OR 2.84; 95% CI 1.35-5.97; P = 0.006), nephrotoxic chemotherapy within the previous 3 months (OR 3.84; 95% CI 1.67-8.84; P = 0.002) and sepsis (OR 2.74; 95% CI 1.30-5.77; P = 0.008). Renal recovery at Day 90 was inversely related to AKI severity. ICU, hospital and Day-90 mortality were 15, 29 and 37%, respectively. Factors independently associated with ICU mortality were: total serum protein (OR per 10 g/L, 0.44; 95% CI 0.23-0.86; P = 0.02) and SAPS II (OR 1.04; 95% CI 1.01-1.07; P = 0.02), while Day-90 mortality was associated with performance status 3-4 (OR 6.59; 95% CI 2.42-18; P < 0.001) and total serum protein (OR 0.60; 95% CI 0.38-0.94; P = 0.02). Conclusions: AKI in patients with solid tumours was frequent and renal recovery gradually decreased in proportion to AKI severity. However, AKI was not independently associated with a higher short-term mortality.

Brain Gray Matter MRI Morphometry for Neuroprognostication After Cardiac Arrest.

OBJECTIVES: We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting. DESIGN: Prospective cohort study. SETTING: Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy). PATIENTS: High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem. CONCLUSIONS: These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.

The optimal time between clinical brain death diagnosis and confirmation using CT angiography: a retrospective study.

BACKGROUND: In several countries, a computed tomography angiography (CTA) is used to confirm brain death (BD). A six­hour interval is recommended between clinical diagnosis and CTA acquisition despite the lack of strong evidence to support this interval. The aim of this study was to determine the optimal timing for CTA in the confirmation of BD. METHODS: This retrospective observational study enrolled all adult patients admitted between January 2009 and December 2013 to the intensive care units of a French university hospital with clinically diagnosed BD and at least one CTA performed as a confirmatory test. The CTAs were identified as conclusive (e.g. yielding confirmation of BD) or inconclusive (e.g. showing persistent brain circulation). RESULTS: One hundred and four patients (sex ratio M/F 1.8; age 55 years [41­64]) underwent 117 CTAs. CTAs confirmed cerebral circulatory arrest in 94 cases yielding a sensitivity of 80%. Inconclusive CTAs were performed earlier than conclusive ones (2 hours [1­3] vs. 4 hours [2­9], P=0.03) and were associated with decompressive craniectomy (5 cases [23%] vs. 6 cases [7%], P=0.05) and the failure to complete full neurological examination (5 cases [23%] vs. 4 cases [5%], P=0.02). Six hours after BD clinical diagnosis, the proportion of conclusive CTA was only 51%, with progressive increase overtime with more than 80% of conclusive CTA after 12 hours. CONCLUSIONS: A 12­hour interval might be appropriate in order to limit the risk of inconclusive CTAs.

Cerebral and extracerebral vulnerability to hypoxic insults after diffuse traumatic brain injury in rats.

The post-traumatic brain vulnerability suggests that after traumatic brain injury (TBI), the brain may be more susceptible to posttraumatic hypoxic insults. This concept could be extended to 'peripheral' organs, as non-neurologic organ failure is common after TBI. This study aims to characterize and quantify cerebral and extracerebral tissue hypoxia with pimonidazole resulting from a standardized hypoxia-hypotension (HH) phase occurring after a diffuse experimental TBI in rats. Rats were allocated to Sham (n=5), TBI (n=7), HH (n=7) and TBI+HH (n=7) groups. Then, pimonidazole was injected and brain, liver, heart and kidneys were analysed. In the cerebral cortex, post-treatment hypoxia was higher in TBI+HH group than Sham group (p=0.003), HH group (p=0.003) and TBI group (p=0.002). Large trends in thalamus, hippocampus and striatum for the TBI+HH group compared to the other groups were observed. For the heart and liver, the 4 groups were comparable. For the kidneys, post-treatment hypoxia was higher in the TBI group compared to the Sham and HH groups, but not more than TBI+HH group. This study reveals that a posttraumatic hypoxic insult occurring after a severe TBI has major hypoxic consequences on brain structures. However, TBI by itself appears to induce renal hypoxia that is not enhanced by posttraumatic hypoxic insult.

Clinical features of life-threatening complications following autologous stem cell transplantation in patients with lymphoma.

Toxic effects of high dose therapy (HDT) combined with autologous stem cell transplantation (ASCT) can lead to life-threatening conditions that may require intensive care unit (ICU) admission. We conducted a retrospective observational study over a 10-year period of all patients admitted to the ICU within 3 months after HDT/ASCT for lymphoma. Among the 532 patients treated by HDT/ASCT at our hospital, 27 (5%) were admitted to the ICU. Infections accounted for 88% (n = 24) of diagnoses, in whom 50% were microbiologically documented. Primary sources of infections were neutropenic enterocolitis (n = 9, 33%) and pneumonia (n = 9, 33%). Bacteria were identified in 83% of documented infections. ICU mortality was 18.5% (n = 5), representing 0.9% of the 532 patients. Among the 22 ICU survivors, 72.7% (n = 16) were alive and in complete remission 6 months after ICU discharge. In our experience, maximal intensive care support is justified for HDT/ASCT recipients with severe complications.